Effects of Local Anesthetics on Liposomal Membranes Determined by Their Inhibitory Activity of Lipid Peroxidation

[Image: see text] In this study, we investigated the effects of drugs on membrane function in which lipid peroxidation was inhibited by the antioxidant Trolox (TRO) in liposomes containing egg yolk lecithin. Local anesthetics (LAs), such as lidocaine (LID) and dibucaine (DIB), were used as model drugs. The effect of LAs on the inhibitory activity of TRO was evaluated by calculating the pI(50) from the inhibition constant K calculated by curve fitting. pI(50)(TRO) indicates the strength of TRO membrane protective function. pI(50)(LA) indicates the strength of LA activity. LAs inhibited lipid peroxidation in a dose-dependent manner and decreased pI(50)(TRO). The effect of DIB on pI(50)(TRO) was 1.9 times more than that of LID. This result indicated that LA may improve the fluidity of the membrane, which may facilitate the migration of TRO from the membrane to the liquid phase. As a result, TRO is less likely to suppress lipid peroxidation within the lipid membrane, possibly resulting in a decrease in pI(50)(TRO). The effect of TRO on pI(50)(LA) was found to be similar in both, indicating that it did not depend on the type of the model drug. These results suggest that our developed procedure successfully quantified the effects of LAs on lipid membrane functions. We were able to obtain the characteristics of model drugs independent of TRO by simultaneously measuring and analyzing the lipid peroxidation inhibitory activities of TRO and model drugs in liposomes.